Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)—a serum prot...

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Main Authors: Li, Jieyi, Chanda, Dipanjan, van Gorp, Patrick J., Jeurissen, Mike L. J., Houben, Tom, Walenbergh, Sofie M. A., Debets, Jacques, Oligschlaeger, Yvonne, Gijbels, Marion J. J., Neumann, Dietbert, Shiri-Sverdlov, Ronit
Format: Online
Language:English
Published: Public Library of Science 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042385/
id pubmed-5042385
recordtype oai_dc
spelling pubmed-50423852016-10-27 Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model Li, Jieyi Chanda, Dipanjan van Gorp, Patrick J. Jeurissen, Mike L. J. Houben, Tom Walenbergh, Sofie M. A. Debets, Jacques Oligschlaeger, Yvonne Gijbels, Marion J. J. Neumann, Dietbert Shiri-Sverdlov, Ronit Research Article Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)—a serum protein mainly secreted by liver—was shown to inhibit oxidized low-density lipoprotein (OxLDL)/lipopolysaccharides (LPS)-induced inflammation in mouse macrophages. Additionally, MSP could reduce palmitic acid (PA)-induced lipid accumulation and lipogenesis in the HepG2 cell line. Altogether, these data suggest MSP as a suppressor for metabolic inflammation. However, so far the potential of MSP to be used as a treatment for NASH was not investigated. We hypothesized that MSP reduces lipid accumulation and hepatic inflammation. To investigate the effects of MSP in the early stage of NASH, low-density lipoprotein receptor (Ldlr-/-) mice were fed either a regular chow or a high fat, high cholesterol (HFC) diet for 7 days. Recombinant MSP or saline (control) was administrated to the mice by utilizing subcutaneously-implanted osmotic mini-pumps for the last 4 days. As expected, mice fed an HFC diet showed increased plasma and hepatic lipid accumulation, as well as enhanced hepatic inflammation, compared with chow-fed controls. Upon MSP administration, the rise in cholesterol and triglyceride levels after an HFC diet remained unaltered. Surprisingly, while hepatic macrophage and neutrophil infiltration was similar between the groups, MSP-treated mice showed increased gene expression of pro-inflammatory and pro-apoptotic mediators in the liver, compared with saline-treated controls. Contrary to our expectations, MSP did not ameliorate NASH. Observed changes in inflammatory gene expression suggest that further research is needed to clarify the long-term effects of MSP. Public Library of Science 2016-09-29 /pmc/articles/PMC5042385/ /pubmed/27685150 http://dx.doi.org/10.1371/journal.pone.0163843 Text en © 2016 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Li, Jieyi
Chanda, Dipanjan
van Gorp, Patrick J.
Jeurissen, Mike L. J.
Houben, Tom
Walenbergh, Sofie M. A.
Debets, Jacques
Oligschlaeger, Yvonne
Gijbels, Marion J. J.
Neumann, Dietbert
Shiri-Sverdlov, Ronit
spellingShingle Li, Jieyi
Chanda, Dipanjan
van Gorp, Patrick J.
Jeurissen, Mike L. J.
Houben, Tom
Walenbergh, Sofie M. A.
Debets, Jacques
Oligschlaeger, Yvonne
Gijbels, Marion J. J.
Neumann, Dietbert
Shiri-Sverdlov, Ronit
Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model
author_facet Li, Jieyi
Chanda, Dipanjan
van Gorp, Patrick J.
Jeurissen, Mike L. J.
Houben, Tom
Walenbergh, Sofie M. A.
Debets, Jacques
Oligschlaeger, Yvonne
Gijbels, Marion J. J.
Neumann, Dietbert
Shiri-Sverdlov, Ronit
author_sort Li, Jieyi
title Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model
title_short Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model
title_full Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model
title_fullStr Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model
title_full_unstemmed Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model
title_sort macrophage stimulating protein enhances hepatic inflammation in a nash model
description Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)—a serum protein mainly secreted by liver—was shown to inhibit oxidized low-density lipoprotein (OxLDL)/lipopolysaccharides (LPS)-induced inflammation in mouse macrophages. Additionally, MSP could reduce palmitic acid (PA)-induced lipid accumulation and lipogenesis in the HepG2 cell line. Altogether, these data suggest MSP as a suppressor for metabolic inflammation. However, so far the potential of MSP to be used as a treatment for NASH was not investigated. We hypothesized that MSP reduces lipid accumulation and hepatic inflammation. To investigate the effects of MSP in the early stage of NASH, low-density lipoprotein receptor (Ldlr-/-) mice were fed either a regular chow or a high fat, high cholesterol (HFC) diet for 7 days. Recombinant MSP or saline (control) was administrated to the mice by utilizing subcutaneously-implanted osmotic mini-pumps for the last 4 days. As expected, mice fed an HFC diet showed increased plasma and hepatic lipid accumulation, as well as enhanced hepatic inflammation, compared with chow-fed controls. Upon MSP administration, the rise in cholesterol and triglyceride levels after an HFC diet remained unaltered. Surprisingly, while hepatic macrophage and neutrophil infiltration was similar between the groups, MSP-treated mice showed increased gene expression of pro-inflammatory and pro-apoptotic mediators in the liver, compared with saline-treated controls. Contrary to our expectations, MSP did not ameliorate NASH. Observed changes in inflammatory gene expression suggest that further research is needed to clarify the long-term effects of MSP.
publisher Public Library of Science
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042385/
_version_ 1613665938856476672

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